The publications and other material used herein to illuminate the background of the invention are incorporated by reference.
Oxidative stress and free radicals have been implicated in the etiology of a number of diseases, including cancers, coronary heart disease, cerebrovascular disease, type 2 diabetes, hypertension, dementia and cataract. The human body has a number of endogenous free radicals scavenging systems which have genetic variability. The human serum paraoxonase (PON) is an enzyme carried in the high-density lipoprotein that contributes to the detoxification of organophosphorus compounds but also of toxic products of lipid peroxidation.1-9 The paraoxonase hydrolyzes the toxic metabolites of several organophosphorus (OP) insecticides, pesticides and nerve agents.
The PON1 gene is polymorphic in human populations and different individuals also express widely different levels and activities of the paraoxonase enzyme, which is the protein product coded by the gene.3,5-7 
Several polymorphisms are currently known in human PON1. The Gln191 Arg poly-morphism was the first mutation of PON1 reported.3,6 The second one is the Met54Leu.3 Both these polymorphisms have been shown to affect serum PON activity.6,10,11 
Transgenic animals and with lowered paraoxonase activity can be used e.g. to test the effects of organophosphorus compounds, such as insecticides, pesticides and war agents, drugs that affect paraoxonase activity, other antioxidative compounds and drugs, and liver enzyme activity inducing agents.
A lot of methodological work has been done to locate disease-causing genes or candidate genes. However, there are no previous methodological studies concerning the methods of how to promote the search for mutations in a given or known candidate gene. To facilitate the finding of mutant DNA sequences, we developed a new method of phenotype-targeted gene sequencing.